Dr. Shiva NazariAssistant Professor of Pediatric Oncologist & Hematologist

Shahid Beheshti Medical Science UniversityMofid Children’s Hospital

Reduction in thenormal red cell

survival (120 days)

RBC

Disruption membrane

Hemoglobin

Heme Globine

Amino acidsFe Carbon monoxideBiliverdine

UnconjugatedbilirubinLiver

Bilirubin glucuronide(conjugate)

Biliary

Intestine

Protein poolTrans ferrin

Urobilinogen Kidney

Urinaryurobilinogen

RBC

Intervascular disruption

Free hemoglobin

HemeMethemoglobin

Albumin

Hepatoglobin

Hemopexin-Hem

Liver(Hepatocyte)

Hemoglobin

Hemogolobinuria

Methemalbumin Kidney

O2

A. Corpuscular abnormalities Cell membrane abnormalities Enzymes abnormalities Hemoglobin abnormalities

B. Extracorpuscular abnormalities Immune mechanisms Non immune mechanisms

1. Consideration of clinical featuresuggesting hemolytic disease

2. Laboratory demonstration of presence ofhemolytic process

3. Determination of the cause of hemolyticanemia

Suggest a hemolytic process:1. Ethnic factors2. Age factors3. History of anemia, Jaundice, gall stone in family4. Persistent anemia associated with reticylocytosis5. Anemia unresponsive to hematinics6. Splenomegaly7. Hemoglobinuria8. Dark urine

Reduce red cell and evidence accelerated of

hemoglobin catabolism

Evidence of increased erythropiesis

1) Increased unconjugated bilirubin

2) Increased fecal urinary urobilinogen

Signs of Intravascular Hemolysis:

1) Raised plasma hemoglobin2) Hemoglobinuria3) Hemosiderinuria4) Haptoglobin low

1) Reticylocytosis2) MCV increased3) RDW increased4) Increased normoblasts5) Specific morphologic abnormalities

Sickle cells – Target cellsBasophil stippling – Spherocyts

6) Expansion of marrow space in chronic hemolysisProminance of frontal bonesHair – on – end appearance of skullBiconecave vertebrae ( Fish – mouth )

7) Decreased red cell survival ( Cr 51 )

1) Hemoglobine , Hematocrit , RBC count2) Serum hepatoglubin3) RBC survival ( Cr 51 )4) LDH ( Isoenzymes )5) Bilirubin level6) Hemoglobinuria7) Reticulocyts8) Antiglobin test ( Coomb’s test ) + -

A - RBC defect :1) Membrane :- Osmotic fragility- Blood Smear- Autohemolysis

2) Hemoglobin :- Sickiling test- Hemoglobin electrophoresis

( Fetal hemoglobin )3) Enzyme :

- Heinz – body- G6PD , PK ( Specific enzym assay )

B - Aquired hemolytic :- Coomb’s test

- Antibody screening- Blood group - Rh

spherocytosis

Autosomal dominantFamily history in 75 %Incidence 1/5000

1- Dysfunction of RBC skeletal protein

2- Extravascular hemolysis (spleen)

3- Decreased surface -area –volume –ratio

4- Tendency to spherocytosis (reduce flexibility)

5- Cell dehydration

Hemoglobine , Hematocrit , RBC countMCV decreasedMCHC increased Retic(3-15%)Osmotic fragility test

Autohemolysis increased (correct by glucose)

Clinical featuresAnemiaJaundice (depend on rate hemolysis)SplenomegalyNewborn hyperbilirubinemiaGallstones

Treatment

Folic acid supplement (1mg/day)Packed red cell transfusionSplenectomy after 5 year

Glucose 6-Phosphate Dehydrogenasedeficiency( G6PD )

G6PD Pentose Phosphate Pathway

1- Sex linked ( X - Chromosome )

2- Variable intermediate expression (Female )(lyon hypotesis – Random deletion X )

3- 35% - In meditranean

Class I Chronic hemolytic anemia

Class II Intermitent hemolysis (mediterranean)

Class III -Intermitent hemolysis (infection- drug)

Patogenesis1 – Red cell G-6PD activity fall was RBC age

2- glucose metabolism

3- NADPH / NADP

4 - H2O2

5 - Oxidation hemoglubin

Clinical features

Episodes of hemolysis may be produced by: Drugs Fava bean Infection

1- Acute self limiting hemolytic anemia2- Hemoglubinuria3- Heinz bodies4- Bliste cell ,sphrocyt5- Reticylotosis6- Hemoglubine normal between episodes7- Blood transfusion required8 - Acute renal failure9 - Neonatal jundice10- Chronic hemolysis ( European )

-In creased autohemolysis ( Not correct )

-Splenomegaly

Treatment1 – Aviodance

2 – Transfusion packed red blood

- Hb 7 g / dL- Persistent hemoglubinuria Hb 9 g / dL

Classification of Immune hemolyticanemia

A – Autoimmune- Associated with warm antibodies ( IgG )- Associated with cold antibodies (IgM)

B – Isoimmune-Hemolytic disease of the newborn- Rh & ABO incompatibility

C - Drug induced- Immune complexes to RBC membrane- Adsorption of drug to RBC- Autoantibody to drug ( Insulin , antihistamine , Sulphanamid )